rs2838735

chr21-44915367-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000211.5(ITGB2):c.-3-4582A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,956 control chromosomes in the GnomAD database, including 10,846 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10846 hom., cov: 31)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

Genes affected

ITGB2 (HGNC:6155): (integrin subunit beta 2) This gene encodes an integrin beta chain, which combines with multiple different alpha chains to form different integrin heterodimers. Integrins are integral cell-surface proteins that participate in cell adhesion as well as cell-surface mediated signalling. The encoded protein plays an important role in immune response and defects in this gene cause leukocyte adhesion deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.-3-4582A>G		intron_variant		ENST00000652462.1
ITGB2	NM_001127491.3	c.-3-4582A>G		intron_variant
ITGB2	NM_001303238.2	c.-253-4582A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.-3-4582A>G		intron_variant			NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54797 AN: 151838 Hom.: 10831 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.361 AC: 54809 AN: 151956 Hom.: 10846 Cov.: 31 AF XY: 0.358 AC XY: 26607 AN XY: 74254

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.402

Alfa AF: 0.418 Hom.: 28170

Bravo AF: 0.370

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.3
Dann	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2838735; hg19: chr21-46335282;